The balance of risks and benefits associated with hormone therapy for menopause may need to be re-evaluated in light of a new study that reinforces mounting concerns over breast cancer risk.
Researchers in the Public Health Sciences Division report that estrogen, whether taken alone or in combination with progestin, resulted in a 70 percent increase in breast cancer risk among postmenopausal women - a risk of 425 cancers per 100,000 women (nearly one half of 1 percent) vs. only 250 cancers per 100,000 women (one quarter of 1 percent).
"Based on our findings and prior research by other groups, the evidence is now quite strong that both types of hormone-replacement therapy increase a woman's risk of breast cancer," said Dr. Emily White, senior author of the study.
White cautioned, however, that no definitive conclusions can be drawn until results are tabulated from a massive Women's Health Initiative (WHI) study on hormone-replacement therapy.
Her recent study, published in the Feb. 13 issue of the Journal of the American Medical Association, was led by graduate student Dr. Chi-Ling Chen, directed by White, Dr. Noel Weiss and Dr. Polly Newcomb of PHS, and Dr. Bill Barlow of the University of Washington Biostatistics Department and Group Health Cooperative of Seattle.
Millions of menopausal American women each year turn to HRT for relief of hot flashes and prevention of bone loss and heart disease. But over the last several years, several studies have indicated a link between HRT and breast cancer and produced conflicting evidence on benefits for cardiovascular disease.
Group Health enrollees
To confirm and extend prior research on hormonal effects on cancer risk, Hutch scientists evaluated 705 postmenopausal women enrolled in Group Health Cooperative who were 50 to 74 years of age and had primary invasive breast cancer diagnosed between July 1, 1990, and Dec. 31, 1995. A group of 692 randomly selected, aged-matchedfemale Group Health members was used as a comparison population.
Breast cancer cases were divided into two groups, based on cell and tissue examination: lobular cancers (91 cases) and nonlobular (primarily involving the breast ducts) cancers (614 cases).
White said the method used to obtain hormone usage data for the women in the Hutch study introduced fewer biases than previous analyses.
"Rather than rely on a woman's memory, we used Group Health's computerized pharmacy database," she said. "This allowed us to obtain accurate, detailed information about all prescriptions dispensed from Group Health pharmacies, including date, dosage, formulation, pill quantity and route of administration."
Long-term HRT risk
Overall, the investigators found a 70 percent increased risk of breast cancer among recent long-term users of HRT, defined as women who have taken hormones for five of the six years prior to cancer diagnosis.
In terms of absolute risk, this translates into one quarter of 1 percent risk of breast cancer per year for women not on HRT, or 250 cancers per 100,000 women, compared to nearly one half of 1 percent risk for women who have recent long-term HRT use, or 425 breast cancers per 100,000 women.
White said the risk increased most for lobular breast cancer, a rarer form of the disease. For lobular cancer, both recent long-term use of either type of HRT and current use of combined therapy led to a three- to fourfold increased risk, a finding that builds on studies by PHS' Dr. Christopher Li.
Women who underwent long-term use of either form of HRT were also about one-and-a-half times more likely than non-users to be diagnosed with the more common ductal form of breast cancer.
Lobular cancer can be a concern because lobular carcinomas are relatively more difficult to detect by manual examination and harder to diagnose by mammography. However, this should not change screening practices because women on HRT who are diagnosed with cancer are still much more likely to be have the ductal type.
Despite the recent study's results, White said she and others await definitive conclusions from the massive WHI study on HRT use.
"We'll have a lot more data about the risks and benefits of hormone therapy when WHI concludes in the next two or three years," she said. "That study began 10 years ago when there was much less concern about risk of hormone use. It will provide information on breast and other cancers as well as fractures and cardiovascular disease."
White said that she and her colleagues are not making recommendations about how doctors should advise their patients.
"I believe we shouldn't put the onus on every doctor to evaluate this and other studies on hormone-replacement therapy," she said. "We need national studies such as the WHI and panels of experts to assess all risks and to come up with a set of guidelines that both doctors and patients can look to for guidance."